A practical method to determine the site of unknown primary in metastatic neuroendocrine tumors

Jessica E Maxwell; Scott K Sherman; Kristen M Stashek; Thomas M O'Dorisio; Andrew M Bellizzi; James R Howe

doi:10.1016/j.surg.2014.08.008

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A practical method to determine the site of unknown primary in metastatic neuroendocrine tumors

Journal article

Open access

Peer reviewed

A practical method to determine the site of unknown primary in metastatic neuroendocrine tumors

Jessica E Maxwell, Scott K Sherman, Kristen M Stashek, Thomas M O'Dorisio, Andrew M Bellizzi and James R Howe

Surgery, Vol.156(6), pp.1359-1366

12/2014

DOI: 10.1016/j.surg.2014.08.008

PMCID: PMC4254437

PMID: 25456909

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https://www.ncbi.nlm.nih.gov/pmc/articles/4254437View

Open Access

Abstract

The site of a primary neuroendocrine tumor (NET) tumor is unknown before treatment in approximately 20% of small bowel (SBNET) and pancreatic (PNET) cases despite extensive workup. It can be difficult to discern a PNET from an SBNET on hematoxylin and eosin stains, and thus, more focused diagnostic tests are required. Immunohistochemistry (IHC) and gene expression profiling are two methods used to identify the tissue of origin from biopsied metastases. Tissue microarrays were created from operative specimens and stained with up to seven antibodies used in the NET-specific IHC algorithm. Expression of four genes for differentiating between PNETs and SBNETs was determined by quantitative polymerase chain reaction and then used in a previously validated gene expression classifier (GEC) algorithm designed to determine the primary site from gastrointestinal NET metastases. The accuracy of the IHC algorithm in identifying the primary tumor site from a set of 37 metastases was 89%, with only one incorrect call. Three other samples were indeterminate as the result of pan-negative staining. The GEC's accuracy in a set of 136 metastases was 94%. The algorithm identified the primary tumor site in all cases in which IHC failed. Performing IHC, followed by GEC for indeterminate cases, identifies accurately the primary site in SBNET and PNET metastases in virtually all patients.

Immunohistochemistry

Neoplasms, Unknown Primary - genetics

Intestine, Small

Humans

Male

Pancreatic Neoplasms - genetics

Gene Expression Profiling

Intestinal Neoplasms - secondary

Sampling Studies

Neuroendocrine Tumors - genetics

Pancreatic Neoplasms - secondary

Algorithms

Microarray Analysis

Neuroendocrine Tumors - secondary

Sensitivity and Specificity

Female

Retrospective Studies

Biopsy, Needle

Intestinal Neoplasms - genetics

Neoplasms, Unknown Primary - pathology

Details

Title: Subtitle: A practical method to determine the site of unknown primary in metastatic neuroendocrine tumors
Creators: Jessica E Maxwell - Department of General Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
Scott K Sherman - Department of General Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
Kristen M Stashek - Department of Pathology, University of Pennsylvania, Philadelphia, PA
Thomas M O'Dorisio - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
Andrew M Bellizzi - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA
James R Howe - Department of General Surgery, University of Iowa Carver College of Medicine, Iowa City, IA. Electronic address: james-howe@uiowa.edu
Resource Type: Journal article
Publication Details: Surgery, Vol.156(6), pp.1359-1366
DOI: 10.1016/j.surg.2014.08.008
PMID: 25456909
PMCID: PMC4254437
NLM abbreviation: Surgery
ISSN: 0039-6060
eISSN: 1532-7361
Publisher: United States
Grant note: 5T32-CA148062-03 / NCI NIH HHS T32 CA148062 / NCI NIH HHS
Language: English
Date published: 12/2014
Academic Unit: Pathology; Surgery; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984047740702771

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